Chokri Ben Lamine: Key types of TMA in pregnancy and management

Chokri Ben Lamine, Adult Hematology, Stem Cell Transplantation and Cellular Therapy Assistant Consultant at King Faisal Specialist Hospital and Research Center shared a post on X:

“Key Types of TMA in Pregnancy and Management.

 Thrombotic Thrombocytopenic Purpura (TTP):

Cause: Severe ADAMTS13 deficiency (<10%) leading to uncontrolled platelet aggregation.

Diagnosis:

• ADAMTS13 activity <10%.
•  ADAMTS13 IgG titers.
• Genetic mutational analysis in congenital TTP (cTTP).

Treatment:

• Immune TTP (iTTP): Plasma exchange (PEX) + corticosteroids.
• Congenital TTP (cTTP): Plasma infusions.

What’s New:

Caplacizumab, a VWF-blocking monoclonal antibody, is now used in refractory iTTP to prevent microthrombi.

HELLP Syndrome (Hemolysis, Elevated Liver Enzymes, Low Platelets):

Cause: Severe endothelial dysfunction due to placental ischemia, leading to hemolysis, liver dysfunction, and thrombocytopenia.

Diagnosis:

• LDH >600 IU/L (hemolysis).
• AST/ALT ≥2x ULN (liver dysfunction).
• Platelet count <100,000.

Treatment:

• Deliver the fetus and placenta as soon as possible.
• Avoid delaying delivery in HELLP as maternal and fetal risks increase rapidly.

What’s New:

• Differentiation from CM-TMA: Use serum creatinine (>1.9 mg/dL) and LDH (>600 IU/L) thresholds.
• Advanced testing like sFlt-1/PIGF ratio may help differentiate HELLP from preeclampsia.

Complement-Mediated TMA (CM-TMA):

Cause: Dysregulation of the complement system due to genetic mutations or autoantibodies (e.g., anti-FH), leading to endothelial damage and platelet activation .

Diagnosis:

• Genetic testing for complement proteins (e.g., C3, CFB mutations).
• Anti-FH antibody titers.

Treatment:

• C5 inhibitors (eculizumab/ravulizumab) block complement activation.
• Plasma exchange is used if C5 inhibitors are unavailable, though efficacy is limited.

What’s New:

• Ravulizumab approved for postpartum CM-TMA.
•  Antiphospholipid Syndrome (APS):

Cause: aPL antibodies (LA, aCL, β2GPI) cause endothelial dysfunction and thrombosis.

Diagnosis:

• aPL antibody titers (persistent positivity).
• History of thrombotic or obstetric complications.

Treatment:

• LMWH + aspirin for pregnancy prophylaxis.
• IVIG in recurrent pregnancy losses despite anticoagulation.

What’s New:

• Trials for novel biologics targeting B cells (anti-CD20), BAFF, and complement pathways.

What’s New in TMA in Pregnancy?

Caplacizumab:

• Blocks platelet-VWF interaction, preventing microthrombi in iTTP.
• Refractory cases have shown improvement with its use.

 Recombinant ADAMTS13:

• Promising in congenital TTP.
• Achieved near-complete normalization of ADAMTS13 activity during pregnancy trials.

 sFlt-1/PIGF Ratio:

• Differentiates preeclampsia from HELLP syndrome or CM-TMA.
• A ratio >40 predicts severe PE and adverse maternal outcomes.

Ravulizumab:

• Long-acting C5 inhibitor now approved for CM-TMA.
• Offers postpartum efficacy in complement-mediated cases.

 Novel Biologics:

• Anti-CD20 (obinutuzumab), anti-TNF (adalimumab, certolizumab), and others under investigation for APS and CM-TMA.

Key Differentiators in TMA Types:

• TMA Type Diagnosis Key Treatment.
• TTP ADAMTS13 <10%, IgG titers PEX + steroids.
• HELLP LDH >600, AST/ALT >2x ULN, Platelets <100k Deliver fetus & placenta.
• CM-TMAGenetic testing, Anti-FH antibodies C5 inhibitors or plasma exchange.
• APSaPL antibody titers (LA, aCL, β2GPI) LMWH + aspirin, IVIG for losses.

Key Exam and Clinical Tips:

• TTP: Caplacizumab for refractory cases; know ADAMTS13 criteria.
• HELLP: Immediate delivery is key; delay worsens outcomes.
• CM-TMA: Complement activation = C5 inhibitors like eculizumab/ravulizumab.
• APS: Focus on prevention with LMWH/aspirin during pregnancy.
• Overlap awareness: Distinguish TTP, HELLP, and CM-TMA with lab markers

From:

• Thrombotic Microangiopathy in Pregnancy.
• Current Understanding and Management.
• Strategies by Manuel Urra and al.”

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